丹参叶水提物对小鼠抗氧化药效学研究

目的 研究丹参叶对D-半乳糖与乙醇诱导的小鼠氧化模型的抗氧化作用。方法 分别建立D-半乳糖与50%乙醇氧化损伤小鼠模型，雄性小鼠120只，各模型组60只，并按其体重随机分为6组：对照组、模型组、丹参叶水提物低、中、高剂量组、抗坏血酸Vc组。通过测定小鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、蛋白质羰基(PC)、总抗氧化能力(T-AOC)、还原型谷胱甘肽(GSH)的水平，研究丹参叶水提物的体内抗氧化活性。结果 丹参叶水提物能显著提升小鼠机体内SOD抗氧化酶的活力与T-AOC总抗氧化能力，增加还原型谷胱甘肽GSH含量(P<0.01);显著降低血清中MDA与PC含量(P<0.01)。结论 丹参叶水提物对D-半乳糖与50%乙醇氧化损伤模型小鼠有一定的抗氧化作用。     

白花蛇舌草醇提物抗氧化活性的研究

目的探讨潮汕野生药用植物白花蛇舌草醇提物在小白鼠体内的抗氧化活性。方法将白花蛇舌草80%乙醇提取物设置为低、中、高3个剂量(0.5、1、2 g·kg-1),给小白鼠每日灌胃1次,对照组给予生理盐水,连续14 d。末次给药禁食24 h后,取小白鼠血样以检测血清中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)含量。取小白鼠肝脏及脑组织,检测总抗氧化能力(T-AOC)、过氧化氢酶(CAT)、谷胱甘肽过氧化氢酶(GSH-Px)、SOD及MDA等抗氧化指标,所有指标均采用试剂盒方法进行测定。结果与对照组相比,高剂量组白花蛇舌草醇提物能明显提高小鼠血清SOD、肝组织中SOD、CAT、GSH-Px、T-AOC及脑组织中CAT、GSH-Px与T-AOC等抗氧化酶的活性,能显著降低小鼠血清、肝脏及脑组织中脂质过氧化产物MDA的水平。其中肝脏组织的指标变化更为明显,尤其是SOD活性的增高,各给药组相比对照组,差异均有统计学意义,各给药组之间差异也有统计学意义,呈现一定的量效关系。结论潮汕野生药用植物白花蛇舌草醇提物在小白鼠体内具有一定的抗氧化活性,就血清、肝脏和脑组织来讲,白花蛇舌草醇提物可以明显提高肝脏的抗氧化能力。     

贯叶连翘耐缺氧及抗氧化作用的实验研究

目的探讨贯叶连翘耐缺氧及其抗氧化作用。方法 20只昆明种小白鼠随机分成正常组（10只）和贯叶连翘组（10只）,灌胃给药30min后,应用常压耐缺氧实验观察2组小鼠存活时间,考察贯叶连翘对小鼠缺氧耐受性的影响;30只SD大鼠随机分成正常组、模型组和贯叶连翘组,每组10只,应用D-半乳糖制造大鼠亚急性衰老模型,采用贯叶连翘灌胃给药30d后,检测各组大鼠血清过氧化氢酶（CAT）、超氧化物岐化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）活性及脂质过氧化代谢产物丙二醛（MDA）含量,评价贯叶连翘对模型大鼠抗氧化能力的影响。结果贯叶连翘能明显延长小鼠存活时间,增强CAT、SOD及GSH-PX活性,减少模型大鼠血清MDA含量。结论贯叶连翘具有提高小鼠缺氧耐受性及明显的抗氧化能力。     

梓醇对D-半乳糖致亚急性衰老小鼠学习记忆及脑中相关抗氧化酶活性的影响

目的观察梓醇对D-半乳糖(D-gal)致亚急性衰老小鼠学习记忆及脑组织中相关抗氧化酶活性的影响。方法用D-gal皮下注射制备衰老小鼠模型,同时在前两周和后两周分别皮下注射给予梓醇(2.5 mg/kg),检测小鼠学习记忆能力和大脑皮层、海马中丙二醛(MDA)水平,超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性。结果衰老模型组小鼠空间学习记忆能力下降,逃避潜伏期较正常对照组明显延长,脑中SOD、GSH-PX活性降低,MDA含量增高。给予梓醇预防和治疗后可以改善衰老模型小鼠的学习记忆能力,并显著提高脑中SOD、GSH-PX活性,降低MDA水平。结论梓醇可改善D-gal致衰老小鼠的学习记忆障碍,此作用可能与梓醇的抗氧化作用有关。     

硒化桑葚多糖及其抗氧化活性研究

目的:通过硒化修饰改变桑葚多糖分子结构,并对比研究其体内抗氧化活性.方法:采用水提醇沉法提取桑葚多糖(FMP),硒化修饰FMP,得到桑葚多糖硒化衍生物(FMPs);考察桑葚多糖的体内抗氧化能力,测定小鼠血清和肝脏中MDA、肝脏T-AOC和CAT;建立高脂血症大鼠抗氧化损伤模型,考察FMP及FMPs的抗氧化能力.结果:FMPs及FMP均可以显著提高正常小鼠肝组织CAT活力及T-AOC,降低小鼠血清及肝脏MDA含量,FMPs抗氧化活性明显优于FMP.此外,FMPs及FMP还可以显著降低四氧嘧啶致高脂大鼠的氧化损伤程度,提高其血清SOD活力及肝脏T-AOC,并降低其血清MDA含量.结论:硒化修饰可显著提高桑葚多糖的抗氧化活性.     

附子汤对次声损伤的防护作用

目的研究附子汤对在8Hz、130dB的次声暴露下小鼠大脑的过氧化水平的影响效果。方法将60只BALB/c小鼠分为次声高剂量用药组,次声中剂量用药组,次声低剂量用药组,次声对照组与正常对照组。15d后测试小鼠大脑微结构的变化,谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)的活性以及丙二醛(MDA)的含量。结果次声对照组与正常对照组相比,GSH-PX活力和MDA含量明显升高(P<0.05),SOD活力略有提高(P>0.05)。三组次声用药组与次声对照组相比,GSH-PX与SOD活力明显提高(P<0.05),MDA含量明显降低(P<0.05)。结论在8Hz、130dB的次声暴露下可以导致小鼠脑皮质脂质的过氧化,附子汤可以提升小鼠身体内部的GSH-PX及SOD活力,从而可以清除过量的体内自由基,使得MDA的含量减少,降低了机体的不良反应。     

酢浆草体外抗炎抗氧化检测方法的建立和优化

目的优化和建立酢浆草体外抗炎抗氧化活性的检测方法。方法建立抗氧化、蛋白酶活性抑制和蛋白变性抑制活性的检测方法。比较醇提水沉法和水提醇沉法、不同保存条件下药物的活性。结果优化检测方法后,不同浓度酢浆草样品的检测结果具有高度相关性,表明检测方法高度稳定且准确可靠。经醇提水沉法和水提醇沉法后,酢浆草的抗氧化活性为100%,蛋白变性抑制活性为90%,酶活性抑制活性为50%,两者出峰位置基本一致。醇提水沉法更易快速获得澄清的提取溶液。室温和4℃冷藏时,蛋白变性抑制成分第3天时均下降40%,第7天时下降至无活性;酶活性抑制成分在冷藏时下降比室温条件慢,在第7天时分别下降30%和60%;抗氧化成分在2种保存条件下均有较高活性。结论所建立的方法可用于体外检测酢浆草的抗炎活性。     

木薯叶不同溶剂提取物中芦丁含量测定及抗氧化活性研究

目的 该实验对木薯叶分别用不同溶剂进行萃取,并对不同溶剂提取物中芦丁的含量和抗氧化活性进行比较分析。方法 对木薯叶分别进行水提、95%乙醇醇提,旋蒸浓缩出2种提取物;分别用水和95%乙醇加热回流后得到两种提取液,对两种提取液采用系统溶剂法分别按照石油醚、氯仿、乙酸乙酯、正丁醇的顺序进行萃取,旋蒸浓缩得到8种溶剂提取物,测定出10种提取物中芦丁含量,并采用DPPH自由基体系法对10种提取物进行抗氧化活性比较。结果 不同提取方法提取出的物质中芦丁含量有所差异性,且在相同质量浓度比较下,抗氧化活性顺序为：醇提正丁醇萃取物>醇提乙酸乙酯萃取物>水提乙酸乙酯萃取物>水提正丁醇萃取物>水提物质>水提氯仿萃取物>醇提氯仿萃取物>醇提物质>水提石油醚萃取物>醇提石油醚萃取物。结论 木薯叶不同溶剂提取物中95%乙醇醇提物质中芦丁含量最高,不同溶剂提取物均有具有不同程度的抗氧化活性,其中醇提正丁醇萃取物的抗氧化活性最高,本实验研究可以为天然抗氧化剂的开发利用提供相关的理论依据。     

骆驼刺茎枝粗多糖体内抗氧化活性考察

摘要：目的:研究骆驼刺茎枝粗多糖（ASSBP）对正常及衰老小鼠的体内抗氧化活性。方法:采用正常小鼠及腹腔注射D-半乳糖诱导的衰老模型小鼠,分别测定高、中、低剂量ASSBP对小鼠脾、胸腺等脏器指数、小鼠血清中超氧岐化酶（SOD）、丙二醛（MDA）活力水平、以及对总抗氧化能力（Trolox等效抗氧化能力,TEAC）的影响,并与阳性药物香菇菌多糖进行比较。结果:与空白组相比,ASSBP高、中、低剂量组小鼠脾、胸腺指数明显增高（P<0.05）;与模型组相比,模型+ASSBP中、高剂量组小鼠脾、胸腺指数明显增高（P<0.05）;阳性对照组小鼠脾、胸腺指数高于ASSBP各剂量组（P<0.05）。与空白组相比,ASSBP高、中剂量组小鼠血清SOD水平显著升高（P<0.05）; ASSBP高、中、低剂量组小鼠血清MDA水平显著降低,TEAC水平显著升高（P<0.05）。与模型组相比,模型+ASSBP高、中剂量组小鼠血清SOD水平显著升高（P<0.05）,模型+ASSBP高、中、低剂量组小鼠血清MDA水平显著降低,TEAC水平显著升高（P<0.05）;与模型+阳性药组相比,模型+ASSBP各剂量组小鼠血清SOD、MDA和TEAC水平无明显差异（P>0.05）。结论:ASSBP对正常及衰老小鼠都具有一定的抗氧化活性,且能增强免疫活性。ASSBP中剂量具有良好的体内抗氧化活性,可通过调节免疫活性和抗氧化活性发挥抗衰老作用。     

杨桃根醇提物对糖尿病模型小鼠的血糖及抗氧化能力的影响研究

目的:研究杨桃根醇提物(ACLRE)对糖尿病模型小鼠的血糖及抗氧化能力的影响。方法:通过对小鼠一次性腹腔注射链脲佐菌素复制糖尿病模型。将小鼠分成5组,即正常、模型、格列本脲及ACLRE高、低剂量组,分别灌胃给药14d,在第0、7、14天时测定小鼠的空腹血糖值;并于第14天处死小鼠,测定小鼠血清及肝脏中的超氧化物歧化酶(SOD)及丙二醛(MDA)值。结果:与模型组比较,ACLRE高、低剂量组均能显著降低糖尿病模型小鼠的空腹血糖(P<0.01),且杨桃根醇提物高剂量组小鼠血清及肝脏中的SOD活性升高(P<0.01),MDA含量降低(P<0.01)。结论:ACLRE能显著降低糖尿病模型小鼠血糖,提高机体SOD活性,降低体内MDA含量,从而提高其抗氧化能力,是一种潜在的治疗糖尿病及其并发症的药物。     

葡萄籽提取物原花青素磷脂复合物抗氧化功能的实验研究

目的 探讨葡萄籽提取物原花青素磷脂复合物的抗氧化作用。方法 取大鼠80只,随机分为8组:空白对照组、模型组、原花青素组、大豆磷脂组、维生素C组、原花青素磷脂复合物低、中、高剂量组。每天灌胃1次,连续灌胃30 d。然后用50%乙醇给大鼠一次性灌胃,造成乙醇氧化损伤模型。通过测定大鼠体重,血清和肝组织中丙二醛含量、蛋白质羰基含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性及还原性谷胱甘肽含量的变化,观察葡萄籽提取物原花青素磷脂复合物的抗氧化作用。结果 原花青素磷脂复合物各剂量组的大鼠体重与模型组及空白对照组比较,均无统计学差异(P>0.05)。原花青素磷脂复合物低剂量组大鼠血清和肝组织MDA含量明显低于模型组(P<0.05),血清和肝组织GSH-PX活性明显高于模型组(P<0.05)。与模型组比较,原花青素磷脂复合物中剂量组和高剂量组大鼠血清和肝组织中SOD、GSH-PX活性及GSH含量较模型组显著升高(P<0.05,P<0.01),MDA和蛋白质羰基含量明显降低(P<0.05,P<0.01)。结论 葡萄籽提取物原花青素磷脂复合物具有显著地抗氧化作用。     

2种藏紫草体外抗氧化及抗菌活性比较

目的 比较长花滇紫草和团花滇紫草75%乙醇提取物的体外抗氧化及抗菌活性。方法 采用ABTS法、FRAP法、邻苯三酚自氧化法测定体外抗氧化能力，并采用肉汤连续稀释法初步考察了2种藏紫草体提取物体外对15种不同菌株的抗菌作用。结果 不同浓度藏紫草的75%乙醇提取物对ABTS自由基和超氧阴离子都有较强的清除能力，与BHT阳性药相当或略高于BHT；总还原力随取物浓度增加而增强；2种藏紫草的提取物对革兰阳性菌有一定的抗菌活性，但对肠杆菌科菌株及铜绿假单胞菌均未见抗菌作用。结论 2种来源的藏紫草均具有一定的体外抗氧化和抗菌作用。     

鱼腥草不同溶剂提取物的抗病毒活性研究

目的 研究鱼腥草不同溶剂提取物体外抗手足口病毒（enterovirus type 71,EV71）、单纯疱疹病毒1型（herpes simplex virus type 1,HSV-1）、呼吸道合胞病毒（respiratory syncytial virus,RSV）、柯萨奇病毒B3型（coxsackie virus type B3,CV-B3）、柯萨奇病毒B5型（coxsackie virus type B5,CV-B5）的活性。方法 采用细胞体外培养技术,建立不同病毒感染模型,用鱼腥草不同溶剂提取物进行治疗,通过细胞融合病变观察法以及MTT比色法检测得到治疗指数（therapeutic index,TI）,以此判定其体外抗病毒活性。结果 体外抗病毒试验结果证明,鱼腥草不同溶剂提取物对HSV-1、EV71抗病毒作用较强,对RSV、CV-B3、CV-B5的效果甚微或无明显作用。鱼腥草醇提物中黄酮类成分含量较高,抗病毒活性相对较高;30%,50%,75%乙醇提取物以及水提醇沉处理沉淀物对HSV-1的TI值分别是81.68,67.23,41.91,32.61,均高于阳性对照阿昔洛韦TI值23.43,显示鱼腥草水醇提取物抗HSV-1的活性较强;75%,50%,30%乙醇提取物对EV71的TI值分别是19.58,20.13,18.84,效果较为显著。结论 研究证实鱼腥草提取物对HSV-1、EV71的抗病毒活性较高,可一定程度为临床应用鱼腥草治疗这2种病毒感染引发的疾病提供参考依据。     

土贝母皂苷甲长循环脂质体的制备及体外性质考察

目的 制备土贝母皂苷甲长循环脂质体（tubeimoside A long-circulating liposomes,TA-LC-Lipo）,并进行体外性质考察。方法 乙醇注入法制备TA-LC-Lipo;采用HPLC测定包封率及体外释放率;通过Marlvern激光粒径分析仪测定粒径和Zeta电位;肉眼观察法和紫外分光光度法评价其溶血作用。结果 确定处方为大豆磷脂浓度10 mg·mL^-1、药脂比1：10、大豆磷脂：胆固醇=4：1、DSPE-PEG 2000的摩尔含量为5%。制备得到的TA-LC-Lipo的平均粒径、PDI、电位、包封率分别为123.0 nm,0.134,-1.20 mV,86.2%。结论 制得的TA-LC-Lipo粒度分布均匀,包封率较高,有较好的缓释作用,并能有效改善土贝母皂苷甲的溶血现象。     

藏药黑果枸杞水提物对运动疲劳所致氧化应激的影响

目的 研究藏药黑果枸杞水提物对运动疲劳所致氧化应激的影响。方法 150只小鼠随机分为3组,分别是泳前组、泳后即刻组和泳后恢复30 min组,每组50只。每组再分为5小组,每组10只,分别是阳性组、空白组和黑果枸杞高、中、低剂量组,灌胃给药30 d后测定小鼠泳前、泳后即刻和泳后恢复30 min后血清中丙二醛（malondialdehyde,MDA）、脂质过氧化物（lipid peroxide,LPO）、活性氧物质（reactive oxygen species,ROS）含量及超氧化物歧化酶（superoxidedismutase,SOD）、过氧化氢酶（catalase,CAT）、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）活性。同时采用体外自由基发生体系,评价藏药黑果枸杞对1,1-二苯基-2-三硝基苯肼（DPPH）、羟基自由基（·OH）、超氧阴离子（O₂^-·）的清除力。结果 黑果枸杞不但可以明显降低泳后及泳后恢复组小鼠血清中MDA、LPO、ROS含量,增加SOD、CAT、GSH-Px活性,而且可以减少DPPH、·OH、O₂^-·的产生。结论 藏药黑果枸杞可明显缓解由于运动疲劳所引起的氧化应激反应。     

Preparation,characterization, and antitumor activities of folate-decorated docetaxel-loaded human serum albumin nanoparticles

Abstract

Context: Docetaxel is now a major antitumor drug in clinical use for the treatment of a variety of tumors. The ethanol/Tween 80 solvent required in the formulation to increase the docetaxel solubility is at least partly responsible for the hypersensitivity reaction, decreased uptake by tumor tissue, and increased exposure to other body compartments.

Objective: The present study was aimed at developing hydrosoluble DTX-FA-HSANPs targeting tumor cells and to investigate antitumor activities of the nanoparticles.

Materials and methods: The DTX-HSANPs were prepared using a desolvation technique and the carboxylic groups of NHS-folate were conjugated with the amino groups of the human serum albumin nanoparticles, and studied their size and zeta potential, drug loading efficiency, surface morphology, release properties in vitro, and antitumor activities.

Results: The spherical nanoparticles obtained were negatively charged with a zeta potential of about ?30?mV and characterized around 150?nm with a narrow size distribution. Drug loading efficiency was approximately 17.2%. The folate-decorated nanoparticles targeted a human hepatoma cell line effectively. The in vitro drug release of DTX-FA-HSANPs in the first 96?h corresponded with the following equation: Q?=?18.87851???0.13866t?+?0.21276t^2???0.00704t³?+?0.0000847854t^4???0.00000034991t⁵ (R^2?=?0.98155). Moreover, the in vitro antitumor activities of DTX-FA-HSANPs were close to the activities of the positive control (docetaxel). The in vivo inhibition ratios of DTX-FA-HSANPs and docetaxel were 66.2% and 59.5%, respectively, at a dose of 5?mg/kg.

Discussion and conclusion: In light of the observed antitumor activities, it would be of considerable interest to collect sufficient data for the clinical application of docetaxel-loaded nanoparticles.     

Free radical scavenging and antioxidant activities of Glinus oppositifolius (carpet weed) using different in vitro assay systems

Glinus oppositifolius (L.) Aug. DC. (Aizoceae), commonly called slender carpet weed, is a prostrate or diffuse herb which acts as stomachic, uterine stimulant, aperient and lochia. It is used traditionally in the treatment of earache, itch and skin diseases. Glinus oppositifolius was extracted with ethanol (70%) and used for the evaluation of various in vitro antioxidant assays which includes H-donor activity, nitric oxide scavenging, superoxide anion scavenging, reducing ability, hydroxyl radical, hydrogen peroxide scavenging, total phenolic content, total flavonoid content, total antioxidant activity by thiocyanate and phosphomolybdenum method, metal chelating, β-carotene bleaching, total peroxy radical assays. The pro-oxidant activity was measured using bleomycin-dependent DNA damage. Ex vivo models such as lipid peroxidation were used to study the antioxidant property of the extract. The various antioxidant activities were compared with suitable standard antioxidants such as ascorbic acid, butylated hydroxyl toluene (BHT), α-tocopherol, curcumin, quercetin and Trolox. The generation of free radicals, viz., O₂^·?, OH^·, H₂O₂, NO^· and peroxyl radicals, were effectively scavenged by the ethanol extract of Glinus oppositifolius. The antioxidant activity depends on concentration and increases with increasing amounts of the extract. The total phenolic content, flavonoid content and total antioxidant activity in Glinus oppositifolius were determined as microgram (μg) pyrocatechol, quercetin and α-tocopherol equivalent/mg, respectively. The extract did not exhibit any pro-oxidant activity when compared with ascorbic acid. The results obtained in this study indicate that Glinus oppositifolius scavenges free radicals and reduces lipid peroxidation, ameliorating the damage imposed by oxidative stress in different disease conditions and serve as a potential source of natural antioxidant.     

不同产地枇杷叶粗提物抑制磷酸二酯酶4活性研究

目的 研究不同产地枇杷叶醇提物对抗炎靶标磷酸二酯酶4（PDE4）的抑制作用。方法 采用体积分数95%乙醇回流提取法提取药材,以标记液体闪烁计数法检测提取物对PDE4的D2亚型靶标（PDE4D2）的抑制活性。结果 测试体系的药物终质量浓度为5 mg/L时,20个样品中9个测试样品的抑制率在80%以下;11个样品的抑制率大于80%,其中8个样品大于90%。结论 不同地枇杷叶醇提物抑制PDE4靶标的活性存在明显差异。     

Prediction of in Vivo Tissue Distribution from in Vitro Data. 2. Correlation Between in Vitro and in Vivo Tissue Distribution of a Homologous Series of Nine 5-n-Alkyl-5-Ethyl Barbituric Acids

Purpose. To evaluate the ability to determine accurate in vivo tissue-to-unbound plasma distribution coefficients (Kpu_e) from in vitro data. Methods. Fresh pieces of fifteen rat tissues/organs were incubated at 37°C with a homologous series of nine barbiturates covering a wide range of lipophilicity (Log P 0.02 to 4.13). Steady-state in vivo Kpu _e values were estimated from the tissue and plasma concentrations following simultaneous dosing by constant rate i.v. infusion of all nine barbiturates. Drug concentrations in the tissues and media were determined by HPLC with UV or mass spectrometric detection. Results. The pharmacokinetics of the barbiturate series following constant rate i.v. infusion indicated a range of clearance (0.49 to 30 ml.min^\-1.kg^\-1) and volume of distribution at steady state (0.51 to 1.9 l.kg^\-1) values. Good agreement was observed between the in vitro and in vivo Kpu values, although for the most lipophilic barbiturates the in vitro data underpredicted the in vivo tissue distribution for all tissues. Conclusions. The in vitro system for predicting the extent of in vivo tissue distribution works well for compounds of widely differing lipophilicity, although for the most lipophilic drugs it may result in an underprediction of in vivo values.     

Pharmacokinetics of the Transdermal Reservoir Membrane System Delivering β-Estradiol: In Vitro/In Vivo-Correlation

Purpose. The aim of our study was to investigate the high fluctuations of Estradiol (E₂) plasma levels transdermally delivered in postmenopausal women by a commercially available membrane controlled reservoir system (MCRS). Methods. The transdermal E₂ flux either out of a complete MCRS or across its membrane out of defined ethanol water mixtures was determined, as well as E₂ plasma profiles in 6 postmenopausal women produced by a MCRS. Results. The transdermal in vitro E₂ flux rate out of a complete MCRS, claimed to deliver 25 g/day, increased steadily, reaching a maximum value of 2.06 ± 0.58 (g/h at 30 to 40 hours and decreased to a rate of about 0.5 (g/h from 60 to 90 hours. No statistically significant differences between plasma profiles calculated from the in vitro investigation and derived from a clinical study could be identified. The E₂ flux in defined ethanol/water mixtures across MCRS-membrane, adhesive and skin layer increased with increasing ethanol concentrations up to a maximum of 227 ± 34 ng/cm²/h at an ethanol concentration of 62.5% (V/V) and decreased with further increase in the volume fraction of ethanol. Conclusions. In vitro as well as in vivo investigations showed high fluctuation of E₂ plasma profiles in postmenopausal women produced by the MCRS. These fluctuations are caused by a non-constant input rate of E₂ which may be due to changing ethanol concentrations in the reservoir of the MCRS.